Objectives: The broad aim of this study is to provide evidence to inform the clinical practice of physicians who provide pharmacologic treatments to children and adolescents with autism. Effective drug treatments may reduce the morbidity frequently associated with this life-long, severe developmental disability. This study will rigorously examine the acute and long-term effectiveness of olanzapine (OLA) and of fluoxetine (FLU) in autistic children between 3 and 17 years old. This project's focus on pediatric subjects will permit analysis of the extent to which age moderates treatment responses. The longitudinal component will examine the impact of sustained drug treatment upon the acquisition of adaptive skills and persistence of maladaptive behaviors in children who are actively developing. Specific Aims: 1). To determine the effectiveness of acute treatment with OLA and FLU in children and adolescents with autism as reflected by efficacy (response status) and tolerability, and to determine if age moderates response to OLA or to FLU in persons with autism; 2) to identify the specific behavioral actions of OLA and FLU in youth with autism; 3) to examine the effects of OLA and FLU on executive functioning in autistic children; 4) to examine the association of pharmacodynamic genetic polymorphisms with treatment response; and 5) to determine the effectiveness and developmental effects of sustained treatment with OLA or FLU in autistic children. Research Design: At least 135 youths (ages 3 to 17 years) with autism will be recruited from across NC. Subjects will be randomly assigned to double blind treatment with one of three treatments: OLA, FLU, or placebo. Dosing will be flexible, with modifications allowed as clinically indicated. Symptom ratings, assessments of developmentally based adaptive behaviors and executive function testing will be performed at baseline and repeated at specific intervals. The acute phase of treatment will last 12 weeks. Subjects with clinically significant improvement and without intolerable side effects will continue maintenance therapy for an additional 40 weeks. Longitudinal assessments of subjects will be done by blind raters for at least one year. Tolerance of the medications will be systematically monitored with special attention to activation and weight gain.